This invention relates to a polymer matrix system capable of holding and retaining various drugs and chemical agents, and designed to slowly release the drugs or other chemicals over a period of time such as several days. Such polymers are especially useful for preparing relatively thin-layer wound dressings which can release antibiotics or other useful drugs over a period of several days, to help promote rapid and proper healing of wounds.
Numerous types of wound dressings have been disclosed in the prior art for placement over an area of wounded or injured skin, including but not limited to wounds caused by burns. The most closely relevant such dressing is disclosed in U.S. Pat. No. 4,563,184 (Korol, 1986). This wound dressing has a synthetic polymer matrix layer which can incorporate any of various types of antibiotics or other chemical compounds, in a manner which allows the antibiotic to be slowly and gradually released onto the wound surface over a period of several days.
As used herein, terms such as sustained release, extended release, gradual release, prolonged release, or timed release all refer interchangeably to a relatively slow and gradual release of a chemical (such as an antibiotic or other wound-treating drug) from a polymer matrix as disclosed herein, in a manner which causes the chemical to be released at sustained rates over at least about 24 hours. In actual practice, the polymer matrices disclosed herein gradually release antibiotic drugs in a sustained manner over about 4 days or more, when shaped into relatively thin layers that are suitable for use as wound dressings. As discussed below, this level of sustained release is more than enough for the vast majority of intended uses, in treating wounds. Longer release times can be achieved, if desired, by methods such as making the layers thicker, or increasing the concentration of the drug(s).
The polymer matrix is created by mixing a suitable polymer, such as poly(2-hydroxy ethyl methacrylate), which is referred to herein by the acronym PHEMA, with a suitable solvent such as polyethylene glycol with a molecular weight of 400, and a hydrogen-bonding plasticizing agent, such as dimethylsulfoxide (DMSO) or diethylformamide, and allowing them to chemically react under suitable conditions. These three ingredients (i.e., the polymer, the solvent, and the plasticizer) are discussed in more detail below. They can be mixed and then spread as a viscous slurry onto any of several types of substrates, such as a sheet of impermeable plastic or porous fabric, to create a pre-formed bandage. The components of the slurry will then undergo a reaction causing a "curing" of the slurry into a solidified yet flexible and pliable layer, as disclosed in U.S. Pat. No. 4,563,184.
This form of cured polymer matrix system was given the designation "DIMAC", using "di" (pronounced with a long I) from the dimethylsulfoxide component, and "mac" from the methacrylate component.
One clinical application of this new polymer matrix drug storage and delivery system uses the antimicrobial agent silver sulfadiazine, the most often used treatment to prevent infections in 2nd and 3rd degree burns. Although the DIMAC polymer system offered substantial promise as an advancement in the art of wound dressings that can slowly release antibiotics, the technology disclosed in that 1986 patent was never commercialized, due to various factors, including several important shortcomings and limitations in the products which resulted from the methods and recipes that were disclosed in the 1986 patent.
In particular, the preformed sheets of the polymer matrix, when formed by the processes described in U.S. Pat. No. 4,563,184 and used with silver sulfadiazine as the drug which was contained in and slowly released by the matrix, exhibited the following shortcomings: (i) they had to be refrigerated during storage; this was explicitly set forth as a binding requirement, in the Food and Drug Administration (FDA) approval which allowed commercial sale and public use of the product; (ii) even when refrigerated they had a shelf life of only 12 months; and, (iii) they emitted a rather unpleasant garlic-like odor, when a dressing was removed from its storage pouch.
In addition, the processing steps needed to properly manufacture the slurry into a fully cured and solidified final product required long periods of time. These lengthy and tedious manufacturing requirements caused serious drawbacks, including: (i) efforts to develop large-scale manufacturing techniques for making commercial quantities of pre-cured sheets were hindered; and, (ii) the final products made by the manufacturing-scale methods that were eventually settled upon were relatively sensitive and vulnerable to process upsets, leading to worthless and wasted products that did not meet the quality control specifications.
For these and other reasons, the initial version of the DIMAC polymer system, which was licensed at one time to a major health care corporation, was never commercialized.
The Inventor of U.S. Pat. No. 4,563,184 (who is also the same applicant herein) has now created substantially improved methods and recipes for creating DIMAC polymer matrix systems, which can be used as wound dressings that will slowly and gradually release antibiotics onto a wound surface over a period of days.
Accordingly, one object of this invention is to disclose methods and recipes which can eliminate the need to refrigerate the resulting wound dressings during storage.
Another object of this invention is to disclose methods and recipes which can double the shelf life of the polymer matrix systems, from one year (for the old formulations) to at least two years, even though refrigeration is no longer required during storage, as it was for products using the old formulations.
Another object of this invention is to disclose methods and recipes which can eliminate or minimize unpleasant odors from the wound dressings.
Another object of this invention is to disclose methods and recipes which can eliminate or minimize yellowing or other unpleasant discoloration which results from aging of the wound dressings created by such methods.
Another object of this invention is to disclose methods and recipes which allow the use of "curing ovens" to cure the liquid slurry into solid resin form, thereby allowing much faster and greatly simplified manufacturing techniques to be used to make the wound dressings.
All of these objects have been accomplished, as will become apparent through the following summary and descriptions of the preferred embodiments. These accomplishments, especially when combined together within a single article of manufacture, provide a number of major advantages and improvements in the polymer systems disclosed herein, and allow various highly advantageous manufacturing techniques, thereby rendering this product well-suited for commercialization and widespread use among burn victims and other patients.